High-throughput screening (HTS)-based spectrophotometric direct peptide reactivity assay (Spectro-DPRA) to predict human skin sensitization potential. (10th October 2019)

• Record Type: Journal Article
• Authors: Cho, Sun-A; An, Susun; Park, Jae-Hak
• Is Part Of: Toxicology letters. Volume 314(2019)
• Page Start: 27
• Page End: 36
• Publication Date: 2019-10-10
• Subjects: Skin sensitization -- Peptide reactivity -- Spectrophotometric -- Animal alternative; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.07.014
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: The skin sensitization potential can be evaluated using spectrophotometric methods for reactivity of chemicals toward peptides. The combination results of cysteine and lysine peptide depletion cut-off showed high accuracy compare to judgement results of human skin sensitization test data. Spectro-DPRA is a convenient and high-throughput in chemico screening animal alternative for skin sensitization. Abstract: Some cosmetic ingredients can act as a chemical hapten to induce an immune response; therefore, evaluating the sensitizing potential of cosmetic ingredients is essential. We previously developed a novel in chemico direct peptide reactivity assay involving a spectrophotometric evaluation (Spectro-DPRA) for animal skin sensitization tests (local lymph node assay; LLNA). Based on previous research, we expanded the test materials to confirm the effectiveness of the Spectro-DPRA method for predicting the animal skin sensitization potential, and further determined the feasibility of the method for estimating the human skin sensitization potential. Spectro-DPRA showed 83.1% or 89.1% accuracy compared to a conventional LLNA or prediction based on human data, respectively, with a combination model using both a cysteine peptide and lysine peptide cut-off. To identify the effect of the lipophilicity of a chemical on predicting the skin sensitization potential, we applied our prediction model to chemicals with a Log Pow range of ―1 to 4. Overall predictability was increased, and the accuracy compared to the LLNA and human data was 91.5% and 94.9%, respectively, in the combination cut-off prediction model. In conclusion, Spectro-DPRA serves as an easy, rapid, and high-throughput in chemico screening method with high accuracy to predict the human skin sensitization potential of chemicals.